BioMed research international, 2019, Vol.2019, p.5196028-11
2019
Details
- Autor(en) / Beteiligte
- Titel
- mTORC2 Regulates Lipogenic Gene Expression through PPARγ to Control Lipid Synthesis in Bovine Mammary Epithelial Cells
- Ist Teil von
- BioMed research international, 2019, Vol.2019, p.5196028-11
- Ort / Verlag
- United States: Hindawi
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Alma/SFX Local Collection
- Beschreibungen/Notizen
- The mechanistic target of rapamycin complex 2 (mTORC2) primarily functions as an effector of insulin/PI3K signaling to regulate cell proliferation and is associated with cell metabolism. However, the function of mTORC2 in lipid metabolism is not well understood. In the present study, mTORC2 was inactivated by the ATP-competitive mTOR inhibitor AZD8055 or shRNA targeting RICTOR in primary bovine mammary epithelial cells (pBMECs). MTT assay was performed to examine the effect of AZD8055 on cell proliferation. ELISA assay and GC-MS analysis were used to determine the content of lipid. The mRNA and protein expression levels were investigated by RT/real-time PCR and western blot analysis, respectively. We found that cell proliferation, mTORC2 activation, and lipid secretion were inhibited by AZD8055. RICTOR was knocked down and mTORC2 activation was specifically attenuated by the shRNA. Compared to control cells, the expression of the transcription factor gene PPARG and the lipogenic genes LPIN1, DGAT1, ACACA, and FASN was downregulated in RICTOR silencing cells. As a result, the content of intracellular triacylglycerol (TAG), palmitic acid (PA), docosahexaenoic acid (DHA), and other 16 types of fatty acid was decreased in the treated cells; the accumulation of TAG, PA, and DHA in cell culture medium was also reduced. Overall, mTORC2 plays a critical role in regulating lipogenic gene expression, lipid synthesis, and secretion in pBMECs, and this process probably is through PPARγ. This finding provides a model by which lipogenesis is regulated in pBMECs.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2314-6133eISSN: 2314-6141DOI: 10.1155/2019/5196028Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6541957
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, Acetyl-CoA Carboxylase - biosynthesis, Animal lactation, Animals, Biosynthesis, Cattle, Cell activation, Cell culture, Cell growth, Cell proliferation, Cell Proliferation - drug effects, Cell Proliferation - physiology, Diacylglycerol O-Acyltransferase - biosynthesis, Docosahexaenoic acid, Enzyme-linked immunosorbent assay, Enzymes, Epithelial cells, Epithelial Cells - metabolism, Fatty Acid Synthase, Type I - biosynthesis, Fatty acids, Female, Fibroblasts, Gene expression, Gene Expression Regulation, Enzymologic - drug effects, Gene Expression Regulation, Enzymologic - physiology, Growth factors, Insulin, Keratin, Laboratories, Lipid metabolism, Lipids, Lipogenesis, Lipogenesis - drug effects, Lipogenesis - physiology, Mammary gland, Mammary Glands, Animal - metabolism, Mechanistic Target of Rapamycin Complex 2 - metabolism, Metabolism, Milk, Morpholines - pharmacology, Oils & fats, Palmitic acid, Peroxisome proliferator-activated receptors, Phosphatidate Phosphatase - biosynthesis, PPAR gamma - antagonists & inhibitors, PPAR gamma - metabolism, Proteins, Rapamycin, Rapamycin-Insensitive Companion of mTOR Protein - antagonists & inhibitors, Rapamycin-Insensitive Companion of mTOR Protein - metabolism, Secretion, Sterols, Synthesis, TOR protein, Transcription factors, Triglycerides